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Differentially expressed proteins identified by TMT proteomics analysis in bone marrow microenvironment of osteoporotic patients

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Abstract

Summary

We applied tandem mass tag (TMT)-based proteomics to investigate protein changes in bone marrow microenvironment of osteoporotic patients undergoing spine fusion. Multiple bioinformatics tools were used to identify and analyze 219 differentially expressed proteins. These proteins may be associated with the pathogenesis of osteoporosis.

Introduction

Bone marrow microenvironment is indispensable for the maintenance of bone homeostasis. We speculated that alterations of some factors in the microenvironment of osteoporotic subjects might influence the homeostasis. This study aimed to investigate the changes in the expression of protein factors in the bone marrow environment of osteoporosis.

Methods

We performed a proteomics analysis in the vertebral body-derived bone marrow supernatant fluid from 8 Chinese patients undergoing posterior lumbar interbody fusion (4 osteoporotic vs. 4 non-osteoporotic) and used micro-CT to analyze the microstructural features of spinous processes from these patients. We further performed western blotting to validate the differential expressions of some proteins.

Results

There was deteriorated bone microstructure in osteoporotic patients. Based on proteomics analysis, 172 upregulated and 47 downregulated proteins were identified. These proteins had multiple biological functions associated with osteoblast differentiation, lipid metabolism, and cell migration, and formed a complex protein–protein interaction network. We identified five major regulatory mechanisms, splicing, translation, protein degradation, cytoskeletal organization, and lipid metabolism, involved in the pathogenesis of osteoporosis.

Conclusions

There are various protein factors, such as DDX5, PSMC2, CSNK1A1, PLIN1, ILK, and TPM4, differentially expressed in the bone marrow microenvironment of osteoporotic patients, providing new ideas for finding therapeutic targets for osteoporosis.

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Acknowledgments

We thank Shanghai Jiao Tong University Affiliated Sixth People’s Hospital (Shanghai, China) for providing us with SkyScan1176 to perform micro-CT and Jingjie PTM BioLab (Hangzhou, China) for the technical support.

Funding

This research is supported by the National Natural Science Foundation of China (81670804), the Science and Technology Program of Hunan Province (2016WK2020) and the Clinical Big Data Project of Central South University.

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Authors and Affiliations

  1. Department of Metabolism and Endocrinology, Hunan Provincial Key Laboratory for Metabolic Bone Diseases, National Clinical Research Center for Metabolic Diseases, the Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China

    Q. Zhou, F. Xie, J. Wang, B. Wu, L. Li & R. Dai

  2. Department of Spine Surgery, the Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China

    B. Zhou & Y. Kang

  3. Osteoporosis and Arthritis Lab, University of Michigan, Ann Arbor, MI, 48109, USA

    Y. Jiang

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  1. Q. Zhou
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Correspondence to R. Dai.

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This study obtained the ethics approval from the ethical committee of the Second Xiangya Hospital.

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Zhou, Q., Xie, F., Zhou, B. et al. Differentially expressed proteins identified by TMT proteomics analysis in bone marrow microenvironment of osteoporotic patients. Osteoporos Int 30, 1089–1098 (2019). https://doi.org/10.1007/s00198-019-04884-0

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